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Macular Degeneration

 

Conventional AMD Treatments

Dry type macular degeneration develops gradually. Supplementation with antioxidants, lutein and zeaxanthin has been suggested by the National Eye Institute and others to slow the progression of dry macular degeneration and, in some patients, improve visual acuity (Tan AG 2008).

Wet macular degeneration can develop more quickly. Patients require treatment soon after symptoms appear. There were no effective treatments for wet macular degeneration until recently. New drugs, called anti-Vascular Endothelial Growth Factor (anti-VEGF) agents, can promote regression of the abnormal blood vessels and improve vision when injected directly into the vitreous humor of the eye (Chakravarthy 2006; Rosenfeld 2006a,b; Anon 2011b). Photodynamic therapy, a systemic treatment used in oncology to eradicate early-stage cancer and reduce the tumor size in end-stage cancers, has also been used to treat wet AMD (Wormald 2007).

Anti-VEGF Medications. Macugen®, Lucentis®, Avastin®, and others are the newest conventional treatments for wet macular degeneration.

VEGF’s main role is to induce new blood vessel formation. It also functions to increase inflammation and cause fluid to leak out of blood vessels. In wet macular degeneration, VEGF stimulates the formation of abnormal blood vessels in the macular area of the retina. Bleeding, leaking, and scarring from these blood vessels eventually causes irreversible damage to the photoreceptors as well as rapid vision loss if left untreated.

All anti-VEGF medications work in a similar fashion. They bind to and inhibit the biologic activity of VEGF. By preventing VEGF’s action, they effectively reduce and prevent the formation of abnormal blood vessels. They also reduce the amount of leakage and therefore reduce swelling in the macula. These actions lead to preservation of vision in patients with wet macular degeneration.

There are three anti-VEGF medications currently being used. Pegaptanib (Macugen®) selectively binds to a specific type of VEGF called VEGF 165, which is one of the most dangerous forms of VEGF (Chakravarthy 2006). Macugen® has been approved by the Food and Drug Administration (FDA) for treatment of wet AMD. It is administered via intraocular injection given every six weeks.

Ranibizumab (Lucentis®) is also FDA-approved to treat wet macular degeneration. Lucentis® inhibits all forms of VEGF. Lucentis® is administered via monthly intraocular injection.

Bevacizumab (Avastin®) is similar to Lucentis® and works to inhibit all forms of VEGF. Avastin® is currently approved by the FDA for metastatic cancer (cancer that has spread to other parts of the body). This drug is commonly used but is not approved by the FDA for wet AMD. The cost of Avastin® is approximately 90% less than the other two agents.

Since VEGF has also been associated with poor prognosis in breast cancer, Avastin® was previously used as treatment. However, the FDA to pulled approval of Avastin® for breast cancer treatment in November 2011after a review of four clinical studies (FDA 2012). These studies concluded that the drug does not prolong breast cancer patients’ overall survival or slow disease progression significantly. Rigorous clinical trials for Avastin® are being performed by the National Eye Institute. Lucentis® is available free in the UK as long as patients meet certain criteria related to vision. Although the mechanisms of action of the anti-VEGF agents are similar, the success rates between the treatments vary. When Macugen® was first approved, seventy percent of patients stabilized with no further severe visual loss (Gragoudas 2004). Macugen® has not been found to improve vision. Lucentis® improved on the results of Macugen®. Ninety-five percent of Lucentis® patients kept their vision, and nearly 40% of Lucentis® patients completing one year of treatment improved their vision to 20/40 or better (Rosenfeld 2006b).

Because Avastin® is used off-label, and its makers do not plan to seek approval of the drug for AMD, it has not been as thoroughly investigated as either Lucentis® or Macugen® (Gillies 2006). However, many retina specialists believe that Avastin’s® efficacy parallels that of Lucentis® (Rosenfeld 2006b).

Lucentis®, Macugen®, and Avastin® are all administered via intraocular injection. In other words, these medications are injected directly into the eye. The injections are given after the surface of the eye has been cleansed and sterilized. Some doctors will give antibiotic drops prior to the injection. Some form of anesthesia is usually administered. This can be given in the form of drops or as a very small injection of anesthetic around the eye. A very fine needle is used and the actual injection takes only a few seconds.

A fourth intraocular anti-VEGF treatment, the VEGF Trap-Eye, approved in November 2011, appears to require fewer injections compared to Lucentis®, while still offering the same improvements in eyesight over a one year period. In trials of more than 2,400 patients, VEGF Trap-Eye intraocular injections dosed every two months offered the same benefits as Lucentis® dosing monthly (Anon 2011b).

Possible complications are retinal detachment and the development of a cataract. High intraocular pressure usually follows the injection but generally resolves within an hour.

Possible adverse effects of intraocular injections occur in less than 1 percent of every 100 injections (Rosenfeld 2006b). When adverse effects occur, however, they can be very serious and threatening to eyesight. One possible adverse reaction is a serious eye infection known as endophthalmitis, an inflammation of the internal tissues of the eyeball, which sometimes leads to loss of vision or severe damage to the eye.

Photodynamic Therapy (PDT) is a systemic treatment used in oncology by a variety of specialists to eradicate premalignant and early-stage cancer and reduce the tumor size in end-stage cancers. PDT involves three key components: a photosensitizer, light, and tissue oxygen.

Photosensitizing agents are drugs that become active when light of a certain wavelength is directed onto the anatomical area where they are concentrated. It is an approved treatment for wet macular degeneration, and is a more widely preferred treatment that takes advantage of certain unique properties of subretinal neovascular vessels.

Compared with normal blood vessels, neovascular tissue appears to retain the light-sensitive medicine used in photodynamic therapy. After the medicine, verteporfin (Visudyne®) for example, has been injected into a peripheral vein, it can detect abnormal blood vessels in the macula and attach itself to the proteins in the abnormal blood vessels. Laser light of specific wavelengths, which activates photosensitive drugs like verteporfin, is focused through the eye for about one minute. When verteporfin is activated by the laser, the abnormal blood vessels in the macula are destroyed. This happens without any damage to surrounding eye tissue. Because normal retinal vessels retain very little verteprofin, the abnormal subretinal vessels are selectively destroyed. Blood or fluid cannot leak out and damage the macula any further (Wormald 2007).

While verteporfin PDT slowed wet AMD progression, newer anti-VEGF therapies have shown vision improvement in many patients. Combination therapies (PDT + corticosteroid + anti-VEGF) have shown some promise, particularly in certain classes of disease (Miller 2010).

Laser Photocoagulation. Laser photocoagulation (LP) is an effective treatment for wet type AMD. However, LP is limited to the treatment of well-defined, or "classic" subretinal neovascularization, present in only 25% of those with wet type AMD (Anon 2011a). In eligible patients, LP is effective at preventing future vision loss, but it cannot restore or improve vision. In addition, choroidal neovascularization can recur after treatment and cause further vision loss (Yanoff 2004). LP has not worked well on atrophic (dry) AMD.

Surgery. Subretinal surgery has been attempted for AMD. Some surgeries were geared toward the removal of blood and the subretinal neovascular membrane. Another type of surgery attempted to physically displace the macula and move it onto a bed of healthier tissue. Overall, research studies show that the results of surgery are disappointing (Bressler 2004). Vision has generally not improved after surgery (Hawkins 2004). Additionally, the frequency and severity of surgical complications were generally thought to be unacceptably high.

In late 2010, the FDA approved a device called the Implantable Miniature Telescope (IMT) to improve vision in some patients with end-stage AMD. The IMT replaces the natural lens through surgery in only one eye and provides 2X magnification. The other eye is used for peripheral vision. In the clinical trials upon which FDA approval was based, at 1 and 2 years post-surgery, 75 percent of patients had an improvement in their visual acuity of two lines of more, 60 percent improved their vision by three lines, and 40 percent had a four-line improvement on the eye chart (Hudson 2008 and www.accessdata.fda.gov).

Each person may respond differently to the various conventional treatments available for macular degeneration. From a patient’s perspective, it is very important to thoroughly understand wet macular degeneration and its treatment in order to be able to discuss a therapeutic plan with his or her doctor. A specific treatment plan should be tailored to each patient’s needs and disease activity.

The advent of anti-VEGF therapies, for example, has been seen as a significant advancement for patients with wet macular degeneration. It is important to speak with a specialist regarding the benefits and side effects of anti-VEGF drugs to determine if they are appropriate for your specific case. It should be noted that there is some speculation, which is not supported by strong human data, that anti-VEGF macular degeneration treatments may exert systemic effects and negatively impact vascular health by “leaking” from the eye. It is, therefore, important to evaluate your cardiovascular health if you are receiving anti-VEGF treatment for macular degeneration. For instance, a person who recently had a heart attack or has extensive atherosclerosis may opt to avoid anti-VEGF treatments in favor of photodynamic therapy or laser photocoagulation. Individuals receiving anti-VEGF treatments should target an optimal cardiovascular health profile, which includes low-density lipoprotein (LDL) levels below 100 mg/dL, fasting glucose between 70-85 mg/dL, etc. For more tips on supporting your cardiovascular health, read our Atherosclerosis and Cardiovascular Disease Protocol.